Abstract：
:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor prognosis and limited therapeutic options. Therefore, there is an urgent need to identify new, safe, and targeted therapeutics for effective treatment of late as well as early stage disease. Plectin-1 (Plec-1) was recently identified as specific biomarker for detecting PDAC at an early stage. We envisioned that multivalent attachment of nanocarriers incorporating certain drugs to Plec-1-derived peptide would increase specific binding affinity and impart high specificity for PDAC cells. Previously, we discovered a novel class of compounds (e.g., quinazolinediones, QDs) that exert their cytotoxic effects by modulating ROS-mediated cell signaling. Herein, we prepared novel QD242-encapsulated polymeric nanoparticles (NPs) functionalized with a peptide to selectively bind to Plec-1. Similarly, we prepared QD-based NPs densely decorated with an isatoic anhydride derivative. Furthermore, we evaluated their impact on ligand binding and antiproliferative activity against PDAC cells. The targeted NPs were more potent than the nontargeted constructs in PDAC cells warranting further development.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Sanna V,Nurra S,Pala N,Marceddu S,Pathania D,Neamati N,Sechi Mdoi
10.1021/acs.jmedchem.5b01571subject
Has Abstractpub_date
2016-06-09 00:00:00pages
5209-20issue
11eissn
0022-2623issn
1520-4804journal_volume
59pub_type
杂志文章abstract：:A series of 3,7-disubstituted-2-(3',4'-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant a...
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